tbuckley/cabot-search huggingface dataset:
Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states
Authors: Thomas R. Müller, Takuya Sekine, Darya Trubach, Julia Niessl, Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Anna Olofsson, Susana Patricia Amaya Hernandez, Yu Gao, Curtis Cai, Gunnar Söderdahl, C. I. Edvard Smith, Anders Österborg, Karin Loré, Margaret Sällberg Chen, Per Ljungman, Hans-Gustaf Ljunggren, Annika C. Karlsson, Sunil Kumar Saini, Soo Aleman, Marcus Buggert
Journal: Science Translational Medicine (2023)

Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA + effector memory subpopulations with stem cell–like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regeneration
Authors: Alazne Moreno-Lanceta, Mireia Medrano-Bosch, Yilliam Fundora, Meritxell Perramón, Jessica Aspas, Marina Parra-Robert, Sheila Baena, Constantino Fondevila, Elazer R. Edelman, Wladimiro Jiménez, Pedro Melgar-Lesmes
Journal: Science Translational Medicine (2023)

Hepatic inflammation is a common trigger of chronic liver disease. Macrophage activation is a predictive parameter for survival in patients with cirrhosis. Ring finger protein 41 (RNF41) negatively regulates proinflammatory cytokines and receptors; however, the precise involvement of macrophage RNF41 in liver cirrhosis remains unknown. Here, we sought to understand how RNF41 dictates macrophage fate in hepatic fibrosis and repair within the inflammatory milieu. We found that RNF41 expression is down-regulated in CD11b + macrophages recruited to mouse fibrotic liver and to patient cirrhotic liver regardless of cirrhosis etiology. Prolonged inflammation with TNF-α progressively reduced macrophage RNF41 expression. We designed a macrophage-selective gene therapy with dendrimer-graphite nanoparticles (DGNPs) to explore the influence of macrophage RNF41 restoration and depletion in liver fibrosis and regeneration. RNF41 expression induced in CD11b + macrophages by DGNP-conjugated plasmids ameliorated liver fibrosis, reduced liver injury, and stimulated hepatic regeneration in fibrotic mice with or without hepatectomy. This therapeutic effect was mainly mediated by the induction of insulin-like growth factor 1. Conversely, depletion of macrophage RNF41 worsened inflammation, fibrosis, hepatic damage, and survival. Our data reveal implications of macrophage RNF41 in the control of hepatic inflammation, fibrosis, and regeneration and provide a rationale for therapeutic strategies in chronic liver disease and potentially other diseases characterized by inflammation and fibrosis.
Hemostatic patch with ultra-strengthened mechanical properties for efficient adhesion to wet surfaces
Authors: Yuting Zheng, Kaavian Shariati, Mahsa Ghovvati, Steven Vo, Nolan Origer, Taichiro Imahori, Naoki Kaneko, Nasim Annabi
Journal: Biomaterials (2023)

Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m3), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.
Azvudine reduces the in-hospital mortality of COVID-19 patients: A retrospective cohort study
Authors: Kaican Zong, Hui Zhou, Wen Li, E Jiang, Yi Liu, Shiying Li
Journal: Acta Pharmaceutica Sinica B (2023)

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure, the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between Azvudine and non-Azvudine groups. There were 1072 patients included in our original cohort. With 1:2 ratio PSM, the Azvudine group included 195 patients and non-Azvudine group included 390 patients. The results showed that Azvudine treatment was associated with improved in-hospital mortality in overall population (OR 0.375, 95% CI 0.225-0.623, P < 0.001), severe subgroup (OR 0.239, 95% CI 0.107-0.535, P = 0.001), critical subgroup (OR 0.091, 95% CI 0.011-0.769, P = 0.028) in matched cohort with univariate analysis. And there was a significantly lower in-hospital mortality in overall population (11% vs. 24%, P＜0.001), severe sub-group (10% vs. 32%, P < 0.001) and critical sub-group (5% vs. 34%, P = 0.017) in matched cohort. These results suggest Azvudine can reduce in-hospital mortality in overall COVID-19 patients, severe, and critical subgroup population.
Grading Fractures on Foot and Ankle X-rays and MRI Scans in the Active Charcot Foot in Diabetes: How Strong Is the Agreement Between Modalities?
Authors: Oliver Artz, Lisa Meacock, David A. Elias, Michael E. Edmonds, Nina L. Petrova
Journal: Diabetes Care (2023)

OBJECTIVE To compare X-ray and MRI as diagnostic tests of active Charcot neuro-osteoarthropathy (CNO) in diabetes. RESEARCH DESIGN AND METHODS X-rays and MRI scans of 48 participants were rated for severity of fracture (0 = no fracture, 1 = fracture, 2 = collapse/fragmentation), and for absence/presence of bone marrow edema (BME) on MRI and absence/presence of bone injury on X-ray. The agreement between modalities was assessed with tests for symmetry, marginal homogeneity, and κ-coefficients. RESULTS X-ray underscored MRI in grading fractures in the metatarsals (P = 0.05) and tarsals (P &amp;lt; 0.001) and reported as normal 79% of the bones with BME. The agreement between X-ray and MRI for grading severity of fracture was moderate to substantial (κ = 0.53; P &amp;lt; 0.001) and for detecting bone injury, slight to fair (κ = 0.17; P &amp;lt; 0.001). CONCLUSIONS The significant underperformance of X-ray in the assessment of the hot, swollen foot in diabetes should be considered when confirming or refuting the diagnosis of active CNO.
Mapping the neuroethological signatures of pain, analgesia, and recovery in mice
Authors: Manon Bohic, Luke A. Pattison, Z. Anissa Jhumka, Heather Rossi, Joshua K. Thackray, Matthew Ricci, Nahom Mossazghi, William Foster, Simon Ogundare, Colin R. Twomey, Helen Hilton, Justin Arnold, Max A. Tischfield, Eric A. Yttri, Ewan St. John Smith, Ishmail Abdus-Saboor, Victoria E. Abraira
Journal: Neuron (2023)
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration
Authors: Li Zhong, Xuan Sheng, Wanbing Wang, Yanzhong Li, Rengong Zhuo, Kai Wang, Lianshuai Zhang, Dan-Dan Hu, Yujuan Hong, Linting Chen, Hengjun Rao, Tingting Li, Muyang Chen, Zhihao Lin, Yun-wu Zhang, Xin Wang, Xiao-Xin Yan, Xiaochun Chen, Guojun Bu, Xiao-Fen Chen
Journal: Immunity (2023)
ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease
Authors: Yingbin Lin, Anlan Lin, Lili Cai, Weibin Huang, Shanzhi Yan, Yuanxiang Wei, Xinglin Ruan, Wenting Fang, Xiaoman Dai, Jinbo Cheng, Jie Zhang, Wanjin Chen, Qinyong Ye, Xiaochun Chen, Jing Zhang
Journal: Molecular Neurodegeneration (2023)

Abstract Background Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer’s disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood. Methods We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice. Results We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner. Conclusion ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Graphical Abstract Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.
The 5-HT1F receptor as the target of ditans in migraine — from bench to bedside
Authors: Dimos D. Mitsikostas, Christian Waeber, Margarita Sanchez-del-Rio, Bianca Raffaelli, Håkan Ashina, Antoinette Maassen van den Brink, Anna Andreou, Patricia Pozo-Rosich, Alan Rapoport, Messoud Ashina, Michael A. Moskowitz
Journal: Nature Reviews Neurology (2023)
Metagenomic assessment of gut microbial communities and risk of severe COVID-19
Authors: Long H. Nguyen, Daniel Okin, David A. Drew, Vincent M. Battista, Sirus J. Jesudasen, Thomas M. Kuntz, Amrisha Bhosle, Kelsey N. Thompson, Trenton Reinicke, Chun-Han Lo, Jacqueline E. Woo, Alexander Caraballo, Lorenzo Berra, Jacob Vieira, Ching-Ying Huang, Upasana Das Adhikari, Minsik Kim, Hui-Yu Sui, Marina Magicheva-Gupta, Lauren McIver, Marcia B. Goldberg, Douglas S. Kwon, Curtis Huttenhower, Andrew T. Chan, Peggy S. Lai
Journal: Genome Medicine (2023)

Abstract Background The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. Methods We profiled 127 hospitalized patients with COVID-19 ( n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. Results Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis , each previously linked to post-acute COVID syndrome or “long COVID,” suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Conclusions Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.
Correction: Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/ PBX3 axis
Authors: Yongyan Wu, Yuliang Zhang, Xiwang Zheng, Fengsheng Dai, Yan Lu, Li Dai, Min Niu, Huina Guo, Wenqi Li, Xuting Xue, Yunfeng Bo, Yujia Guo, Jiangbo Qin, Yixiao Qin, Hongliang Liu, Yu Zhang, Tao Yang, Li Li, Linshi Zhang, Rui Hou, Shuxin Wen, Changming An, Huizheng Li, Wei Xu, Wei Gao
Journal: Molecular Cancer (2023)
Donor-derived CD19-targeted chimeric antigen receptor T cells in adult transplant recipients with relapsed/refractory acute lymphoblastic leukemia
Authors: Ibrahim Aldoss, Samer K. Khaled, Yan Wang, Xiuli Wang, Joycelynne Palmer, Mary C. Clark, Jamie R. Wagner, Jinny Paul, Vibhuti Vyas, Christine E. Brown, Stephen J. Forman
Journal: Blood Cancer Journal (2023)

Donor-derived CD19-targeted chimeric antigen
Prospective validation of dermoscopy-based open-source artificial intelligence for melanoma diagnosis (PROVE-AI study)
Authors: Michael A. Marchetti, Emily A. Cowen, Nicholas R. Kurtansky, Jochen Weber, Megan Dauscher, Jennifer DeFazio, Liang Deng, Stephen W. Dusza, Helen Haliasos, Allan C. Halpern, Sharif Hosein, Zaeem H. Nazir, Ashfaq A. Marghoob, Elizabeth A. Quigley, Trina Salvador, Veronica M. Rotemberg
Journal: npj Digital Medicine (2023)

The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE's sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1-98.9%) and specificity of 37.4% (95% CI: 33.3-41.7%). The dermatologists' ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts' ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.
Correction to: Bioengineered materials with selective antimicrobial toxicity in biomedicine
Authors: Pooyan Makvandi, Hao Song, Cynthia K. Y. Yiu, Rossella Sartorius, Ehsan Nazarzadeh Zare, Navid Rabiee, Wei-Xi Wu, Ana Cláudia Paiva-Santos, Xiang-Dong Wang, Cheng-Zhong Yu, Franklin R. Tay
Journal: Military Medical Research (2023)
Medication abortion via digital health in the United States: a systematic scoping review
Authors: Fekede Asefa Kumsa, Rameshwari Prasad, Arash Shaban-Nejad
Journal: npj Digital Medicine (2023)

Digital health, including telemedicine, has increased access to abortion care. The convenience, flexibility of appointment times, and ensured privacy to abortion users may make abortion services via telemedicine preferable. This scoping review systematically mapped studies conducted on abortion services via telemedicine, including their effectiveness and acceptability for abortion users and providers. All published papers included abortion services via telemedicine in the United States were considered. Articles were searched in PubMed, CINAHL, and Google Scholar databases in September 2022. The findings were synthesized narratively, and the PRISMA-ScR guidelines were used to report this study. Out of 757 retrieved articles, 33 articles were selected based on the inclusion criteria. These studies were published between 2011 and 2022, with 24 published in the last 3 years. The study found that telemedicine increased access to abortion care in the United States, especially for people in remote areas or those worried about stigma from in-person visits. The effectiveness of abortion services via telemedicine was comparable to in-clinic visits, with 6% or fewer abortions requiring surgical intervention. Both care providers and abortion seekers expressed positive perceptions of telemedicine-based abortion services. However, abortion users reported mixed emotions, with some preferring in-person visits. The most common reasons for choosing telemedicine included the distance to the abortion clinic, convenience, privacy, cost, flexibility of appointment times, and state laws imposing waiting periods or restrictive policies. Telemedicine offered a preferable option for abortion seekers and providers. The feasibility of accessing abortion services via telemedicine in low-resource settings needs further investigation.
Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer’s disease
Authors: Cristiano D’Andrea, Federico Angelo Cazzaniga, Edoardo Bistaffa, Andrea Barucci, Marella de Angelis, Martina Banchelli, Edoardo Farnesi, Panagis Polykretis, Chiara Marzi, Antonio Indaco, Pietro Tiraboschi, Giorgio Giaccone, Paolo Matteini, Fabio Moda
Journal: Translational Neurodegeneration (2023)

Abstract Background The current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis. Methods Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS). Results The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD. Conclusions Such analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.
SEESAW: detecting isoform-level allelic imbalance accounting for inferential uncertainty
Authors: Euphy Y. Wu, Noor P. Singh, Kwangbom Choi, Mohsen Zakeri, Matthew Vincent, Gary A. Churchill, Cheryl L. Ackert-Bicknell, Rob Patro, Michael I. Love
Journal: Genome biology (2023)

Detecting allelic imbalance at the isoform level requires accounting for inferential uncertainty, caused by multi-mapping of RNA-seq reads. Our proposed method, SEESAW, uses Salmon and Swish to offer analysis at various levels of resolution, including gene, isoform, and aggregating isoforms to groups by transcription start site. The aggregation strategies strengthen the signal for transcripts with high uncertainty. The SEESAW suite of methods is shown to have higher power than other allelic imbalance methods when there is isoform-level allelic imbalance. We also introduce a new test for detecting imbalance that varies across a covariate, such as time.
Intraductal Papilloma of the Male Breast (Case Report)
Authors: M. A. Ivanyuk, A. B. Abduraimov, G. E. Kvetenadze, E. V. Shivilov, K. S. Arslanov, N. S. Karnaukhov
Journal: Radiology - Practice (2023)

A case of revealing a rare pathology for the mammary glands in men - intraductal papilloma is presented. There is the features of the clinical course, mammography and ultrasound visualization and the results of histology. The final diagnosis of «intraductal papilloma» is established only on the basis of pathomorphological and immunohistochemical studies obtained during excisional biopsy.
The human pangenome reference anticipates equitable and fundamental genomic insights
Authors: Kelly A. Frazer, Nicholas J. Schork
Journal: Cell Genomics (2023)

For the past few years, researchers in the Human Pangenome Reference Consortium (HPRC) have been working to catalog almost all human genomic diversity. Frazer and Schork preview an article recently published in Nature, "A draft human pangenome reference,"1 which represents the initial release of 47 fully phased diploid assemblies of genomes of individuals with diverse ancestries.